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I was considering going to a psychiatrist about the depression I've been experiencing all year, and I would like to be put on medication because I just want to feel normal again and happy. I was just wondering if anyone can tell me their experiences with Wellbutrin.

Thanks in advance,


Some studies have found it useful and found that it returned cognitive functioning to normal. I would also point out that in my research I have not found the drug to be neurotoxic though a select group of people would argue that point.

I would however not recommend taking it for depression or if you have previously used marijuana. Witness:

****Dopamine and Dopamine D2 Receptors and their relationship to depression

"Li-Huei Tsai, Harvard Medical School (HMS) professor of pathology, HMS research fellow Sang Ki Park, and colleagues worked with mice and found a novel function for the molecule Par-4 (prostate apoptosis response 4)--as a binding partner for dopamine receptor D2. When mice deficient in Par-4 were subjected to stress, they showed depression-like behaviors, proposing Par-4-as a molecular link between dopamine signaling and depression. Par-4 was previously implicated as a proapoptotic factor in neurodegenerative diseases such as Alzheimer's disease. These new findings reveal an unexpected role for Par-4 in the dopamine system and present a rare glimpse of molecular mechanisms behind clinical depression."

"In laboratory tests with mice, researchers found prolonged exposure to dopamine through this pathway inactivated a regulatory protein in the brain known as Akt and caused the mice to behave like they were depressed in response to stress."

"The Duke team's previous work suggested that the regulatory protein beta-arrestin 2, normally involved in desensitization of receptor signals, is required for normal dopamine-related behavior. They also found that prolonged stimulation of D2 receptors leads to inactivation of a regulatory protein called Akt.

Furthermore, they showed, Akt inactivation occurred more slowly and was maintained for longer than other similar biochemical events that had previously been observed. However, the mechanism behind that inactivation remained unclear.

In the current study in mice, the Duke team found that Akt inactivation by dopamine involves the formation of a previously unidentified complex containing beta-arrestin 2, Akt and a third protein phosphatase 2A that inactivates Akt. Mice lacking beta-arrestin become less responsive to certain drugs and exhibit abnormalities in behaviors, such as locomotion, associated with dopamine. In addition to the behavioral deficits, the animals also lack normal regulation of Akt, they report.

"These results provide direct physiologically relevant evidence for the emerging concept that beta-arrestin 2 not only controls desensitization but also participates in slow synaptic transmission here by acting as a scaffold for signaling molecules in response to dopamine receptor activation," Caron said.

"The observations also provide an alternative pathway by which dopamine receptor activation leads to the expression of dopamine-associated behaviors." "

High dopamine levels acting upon D2 receptors or insufficient levels of Par-4 at D2 receptors can lead to/cause depression.

****Elevated dopamine D2 receptor expression and depression

Am J Psychiatry 163:1594-1602, September 2006
doi: 10.1176/appi.ajp.163.9.1594
© 2006 American Psychiatric Association

Elevated Putamen D2 Receptor Binding Potential in Major Depression With Motor Retardation: An [11C]Raclopride Positron Emission Tomography Study
Jeffrey H. Meyer, M.D., Ph.D., Heather E. McNeely, Ph.D., Sandra Sagrati, B.Sc., Anahita Boovariwala, B.Sc., Krystle Martin, B.Sc., N. Paul L.G. Verhoeff, M.D., Ph.D., Alan A. Wilson, Ph.D., and Sylvain Houle, M.D., Ph.D.

Effect of Major Depressive Episode on Striatal D2 Binding Potential
"As seen in Figure 1, D2 binding potential in depressed subjects was significantly elevated in every striatal region (ANOVA F=4.99–10.23, df=1, 40, p=0.03–0.002; magnitude: 6% to 8%). Somewhat more motor retardation was seen in the depressed subjects (mean=42.6 taps in 10 seconds) than in the healthy subjects (mean=47.0 taps in 10 seconds) (t=1.8, df=38, p=0.08). In the voxel analysis, D2 binding potential in the depressed subjects was elevated in the entire striatum (Figure 2)."

Figure 1

"Striatal D2 Binding Potential in Depressed Subjects With Motor Retardation
The subgroup of depressed subjects with motor retardation (N=10) exhibited significantly greater motor retardation (mean=37.3 taps in 10 seconds) than did the healthy subjects (mean=47.0 taps in 10 seconds) (t=3.37, df=29, p=0.002). No differences between depression subgroups was found with respect to age, gender, or number of depressive episodes.

As seen in Figure 3, the depressed subgroup with motor retardation had significantly higher D2 binding potential in each putamen region than the healthy subjects (left putamen: F=10.54, df=1, 29, p=0.003 [magnitude 10%]; right putamen: F=6.86, df=1, 29, p=0.01 [magnitude 8%]). In the voxel analysis, D2 binding potential was elevated throughout the striatum in the depressed subjects with motor retardation (Figure 4)."

Figure 3

"Secondary Neuropsychological and Clinical Measures and Regional D2 Binding Potential in Depressed Subjects
Since the D2 binding potential among regions was correlated within individuals, the correlations between other neuropsychological measures and whole striatal D2 binding potential was examined first (Table 2). There were no significant correlations between individual neuropsychological tests and regional D2 binding potential in either group (except for the finger tapping test). In addition, post hoc analyses of clinical measures showed that no other clinical variable (including number of previous episodes, length of current episode, history of antidepressant treatment) was significantly correlated with regional D2 binding potential."

"This is the first study to investigate striatal D2 binding potential in medication-free, nonsmoking depressed subjects. The main findings were that caudate and putamen D2 binding potential were elevated in the depressed group as compared with the healthy group, and that putamen D2 binding potential was most significantly elevated in the depressed subgroup with motor retardation. Moreover, there was a significant correlation between putamen D2 binding potential and motor speed in the depressed group. These findings are important for understanding the pathophysiology of depression because they represent a striatal dopaminergic disturbance during depression that is most prominent when motor retardation is present. This has implications for the monoamine theory of depression. In addition, these findings have important implications for treatment, since this dopamine abnormality may be targeted by dopamine-increasing antidepressants."

Demonstrates that dopamine D2 receptor binding is higher in major depression.

****Wellbutrin causes an upregulation of Dopamine D2 Receptors

1: J Recept Res. 1993;13(1-4):341-54.
Regulation of dopamine receptors by bupropion: comparison with antidepressants and CNS stimulants.
Vassout A, Bruinink A, Krauss J, Waldmeier P, Bischoff S.

Research Department, CIBA-GEIGY Ltd., Basel, Switzerland.

Acute treatment of rats with the antidepressant bupropion increased [3H]spiperone binding to D2 receptors in vivo. This dose- and time-dependent effect was greatest in striatum and minimal in cerebellum and pituitary. A parallel behavioral stimulation occurred in the same rats. Among 21 antidepressants and CNS stimulants tested, only those that activate dopamine (DA) transmission had similar effects: nomifensine, amineptine, methylphenidate, D-amphetamine, amfonelic acid, cocaine, benztropine and GBR 12909. Decreasing DA transmission with reserpine plus alpha-methyl-p-tyrosine prevented the action of bupropion. Finally, bupropion was inactive in vitro and ex-vivo. Therefore, we propose that bupropion and other DA-enhancing agents modify the characteristics of [3H]spiperone binding through the intervention of a dynamic regulation of the D2 receptors by the neurotransmitter itself.

PMID: 8095555 [PubMed - indexed for MEDLINE]

Indicates that acute application of bupropion increases D2 receptor binding/availability and in combination with the prior referenced documents leads to one method via which Wellbutrin could worsten/cause depression with sub-chronic or possibly chronic treatment.

YMMV. Wellbutrin is a NDRI - Noradrenaline/Dopamine reuptake inhibitor and therefore stimulates or acts as an agonist at dopamine D2 receptors potentially making your depression worse. Elevated dopamine D2 receptor levels are also involved in a whole host of psychiatric disorders - Tremors, dementia, memory loss, schizophrenia, depression, anxiety, panic attacks and possibly even depersonalization (though I'm still working on the proof for that one). Mess with dopamine only as a last resort and only with intense research and the advice of a doc who is very knowledgeable.

Wellbutrin and other dopamine agonists have been shown to increase libido. But is it worth loosing your mind in order to have good sex?

Disclaimer - I did have a bad experience with Wellbutrin.